Structures and Polymorphic Interactions of Two Heptad-Repeat Regions of the SARS Virus S2 Protein

Journal Article · Sun Jan 01 04:00:00 EST 2006 · Structure

DOI:https://doi.org/10.1016/j.str.2006.03.007· OSTI ID:914013

Deng, Y; Liu, J; Zheng, Q; Yong, W; Lu, M

Entry of SARS coronavirus into its target cell requires large-scale structural transitions in the viral spike (S) glycoprotein in order to induce fusion of the virus and cell membranes. Here we describe the identification and crystal structures of four distinct a-helical domains derived from the highly conserved heptad-repeat (HR) regions of the S2 fusion subunit. The four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-helix bundle that is likely the final fusogenic form of the protein. When considered together, the structural and thermodynamic features of the four domains suggest a possible mechanism whereby the HR regions, initially sequestered in the native S glycoprotein spike, are released and refold sequentially to promote membrane fusion. Our results provide a structural framework for understanding the control of membrane fusion and should guide efforts to intervene in the SARS coronavirus entry process.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 914013
• Report Number(s): BNL--78581-2007-JA
• Journal Information: Structure, Journal Name: Structure Journal Issue: 5 Vol. 14
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
43 PARTICLE ACCELERATORS
CELL MEMBRANES
CRYSTAL STRUCTURE
GLYCOPROTEINS
MEMBRANES
NSLS
PROTEINS
TARGETS
THERMODYNAMICS
national synchrotron light source